Cellular mechanisms of estrogen hormone action

Estrogen can elicit biological effects through multiple mechanistic modes of action: (1) Estrogen in the circulatory system can interact with multiple receptors on or associated with the cell plasma membrane. [a] G-protein coupled receptor (GPR30) [b] membrane-associated form of ER-alpha. (2) Diffusion of estrogen into the cell nucleus and interactions with nuclear forms of either ER-alpha or ER-beta. Hormone binding to the nuclear ER results in dimerization and binding with coactivator proteins (eg, SRC) to gene regulatory sites on DNA. (3) Ligand-independent activation of the estrogen receptor by intracellular signaling pathways (eg, ERK, MAPK, AKT) that are stimulated by growth factors. EDCs can utilize these modes of action to either mimic as an agonist or antagonize the effects of hormones as shown for estrogen. Refer to UpToDate content on endocrine-disrupting chemicals for additional information.